Regenerative Elastography: Monitoring Soft Tissue Reconstruction

University Of Nebraska Lincoln, Lincoln NE

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Abstract

DESCRIPTION (provided by applicant): Tissue engineering involves time- and sequence-dependent procedures where the final outcome is unknown until the restored tissue is formed and functioning. Monitoring changes in the biomechanical properties during tissue development, maturation, ageing, and the onset of disease is critical to the design of new tissue engineering techniques for tissue repair and regeneration. Non-invasive periodic monitoring of the stiffness of a tissue-engineered construct during tissue growth would enable instantaneous non-destructive means for tissue differentiation and development. Magnetic resonance elastography (MRE) is such a technique that measures the viscoelastic properties of soft biological tissues in a non-invasive manner. MRE generates images that depict shear wave motion from which we can calculate local values of the tissue stiffness. MRE, as currently applied, cannot be used to study small biological tissues, or to image in vivo thin tissue regions, such as articular cartilage with thickness less than 2 mm and distinct structure in sub millimeter layers. Recently, we have extended MRE to the microscopic scale and have referred to it as microscopic MR elastography (<MRE). Such 5MRE studies have used a low frequency acoustic shear wave excitation (so far up to 1 kHz, which is higher than in conventional MRE systems), a strong magnetic field (11.74 T), and high gradient strengths (200 G/cm) to assess tissue mechanical properties with high spatial resolution (34 <m x 34 <m x 500 <m) and improved sensitivity. We validated this technique first using agarose gel composite phantoms, and second in studies of different biological tissues (frog oocyte and tissue engineered fat and bone) in vitro. In each case, analysis of the low amplitude shear wave pattern using isotropic and homogeneous models of the medium allowed the identification of the viscoelastic properties. The goal of this work is to monitor and enhance adipogenesis in tissue engineered fat using microscopic magnetic resonance elastography in vitro and in vivo. In recent work with our tissue engineering collaborators, using mesenchymal stem cells (hMSCs), and biocompatible scaffolds were combined to form substrates for engineered adipogenic tissues. Upon tissue stimulation, with specific adipogenic differentiation factors the tissue engineered constructs changed their mechanical properties as lipid matrix was produced by differentiating hMSCs. Adipogenic tissue became softer as adipogenic matrix production from the adipogenic cells gradually increases with respect to time. The ultimate goal of this project is to integrate tissue engineering with microscopic magnetic resonance elastography to speed the translation of tissue engineering technology in regenerative medicine by providing a real-time, non-invasive monitoring technique to assess tissue development and host tissue integration in vivo. The specific aims are: 1) Optimize <MRE testing protocols of engineered adipogenic tissues and enhance adipogenesis in vitro;2) Develop and build high frequency mechanical actuators for in vivo animal testing;3) Apply <MRE to monitor adipogenic tissue engineered constructs in vivo. PUBLIC HEALTH RELEVANCE: Current cancer treatments usually involve surgery, chemotherapy, or radiation. These treatments play a vital role in saving patient's lives but in breast cancer and head and neck cancer, for example, leave the patient with disfiguration and loss of normal function. Tissue engineering will play a vital role in rehabilitation and full organ restoration. In this project, we are proposing to monitor the tissue engineering process to speed the translation of tissue engineering in regenerative medicine.